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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels

Authors :
Matthew DeFelice
Brendan Blumenstiel
Esa Laurila
Marju Orho-Melander
Lauren Gianniny
Mary Fava
John G. Gibbons
Qicheng Ma
Liselotte Hall
Bob Handsaker
Christopher Newton-Cheh
Joel N. Hirschhorn
Stacey Gabriel
Guillaume Lettre
Wendy Brodeur
Carrie Sougnez
Olle Melander
Maria Sterner
Melissa Parkin
Bo Isomaa
Peter Almgren
Lennart Råstam
Marja-Riitta Taskinen
Claire M. Healy
Marketa Sjögren
Jose C. Florez
Richa Saxena
Johan Holmkvist
Ryan Tewhey
Leif Groop
Margareta Svensson
Kieu Nguyen
Jody Camarata
David Altshuler
Kristin Ardlie
Nancy Chia
Noël P. Burtt
Helen N. Lyon
Delwood Richardson
Joanne M. Meyer
Elizabeth K. Speliotes
Peter Nilsson
Aarti Surti
Mark J. Daly
Ulf Lindblad
Rachel Hackett
Paul I.W. de Bakker
Gung-Wei Chirn
Hemang Parikh
Diane Gage
Rachel Barry
Anna Berglund
Thomas E. Hughes
Marcia M. Nizzari
Sekar Kathiresan
Darrell O. Ricke
Malin Svensson
Jeffrey J. Roix
Benjamin F. Voight
Hong Chen
Casey Gates
Candace Guiducci
Valeriya Lyssenko
Tiinamaija Tuomi
Kristina Bengtsson Boström
Shaun Purcell
Joyce Carlson
Source :
Science (New York, N.Y.). 316(5829)
Publication Year :
2007

Abstract

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D—in a noncoding region near CDKN2A and CDKN2B , in an intron of IGF2BP2 , and an intron of CDKAL1 —and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.

Details

ISSN :
10959203
Volume :
316
Issue :
5829
Database :
OpenAIRE
Journal :
Science (New York, N.Y.)
Accession number :
edsair.doi.dedup.....1473b80ffdfa7faf52f3f3b608ab4016